The objective of this grant proposal is to investigate stem cell physiology in stimulated hemopoiesis using animal models with marrow expansion. We have recently documented the expansion of hemopoietic bone marrow to be a major mechanism for marked neutrophilia observed in mice bearing mammary carcinoma. The mechanisms of bone marrow expansion will be investigated using these tumor bearing mice as a model of sustained and progressive granulocytopoiesis and mice with phenylhydrazine induced anemia as a model of stimulated erythropoiesis. Dynamic changes of stem cells in expanding bone marrow will be investigated by using in vitro and in vivo stem cell assay techniques. We will further explore the relationship of stimulated hemopoiesis and changes in marrow stromal elements using these animal models of marrow expansion. This research will provide new information for the comprehensive understanding of the in vivo regulation of stem cells.